New Method Eradicates Deadly Brain tumors by ‘Starving’ Them of Energy Source

By Hamodia Staff

YERUSHALAYIM – A groundbreaking study at Tel Aviv University has demonstrated the potency of an innovative technique for treating brain cancer in cases where until now patients have had little hope of survival.

The researchers said: “Glioblastoma is an extremely aggressive and invasive brain cancer, for which there exists no known effective treatment. The tumor cells are highly resistant to all known therapies, and, sadly, patient life expectancy has not increased significantly in the last 50 years. Our findings provide a promising basis for the development of effective medications for treating glioblastoma and other types of brain tumors.”

Dr. Lior Mayo, of TAU’s Shmunis School of Biomedicine and Cancer Research, explained the new approach: “Here, we tackled the challenge of glioblastoma from a new angle. Instead of focusing on the tumor, we focused on its supportive microenvironment, that is, the tissue that surrounds the tumor cells.

“Specifically, we studied astrocytes – a major class of brain cells that support normal brain function, discovered about 200 years ago and named for their starlike shape. Over the past decade, research from us and others revealed additional astrocyte functions that either alleviate or aggravate various brain diseases,” he said.

Using an animal model, in which they could eliminate active astrocytes around the tumor, the researchers found that in the presence of astrocytes, the cancer killed all animals with glioblastoma tumors within 4-5 weeks. Applying a unique method to specifically eradicate the astrocytes near the tumor, they observed a dramatic outcome: the cancer disappeared within days, and all treated animals survived. Moreover, even after discontinuing treatment, most animals survived.

Dr. Mayo described how the astrocytes behave: “We found that astrocytes ‘persuade’ immune cells to ‘change sides’ and support the tumor instead of attacking it. Specifically, we found that the astrocytes change the ability of recruited immune cells to attack the tumor both directly and indirectly – thereby protecting the tumor and facilitating its growth.”

The second change through which astrocytes support glioblastoma is by modulating their access to energy – via the production and transfer of cholesterol to the tumor cells.

The malignant glioblastoma cells divide rapidly, a process that demands a great deal of energy. With access to energy sources in the blood barred by the blood-brain barrier, they must obtain this energy from the cholesterol produced in the brain itself – namely in the astrocytes’ ‘cholesterol factory’, which usually supplies energy to neurons and other brain cells. They discovered that the astrocytes surrounding the tumor increase the production of cholesterol and supply it to the cancer cells. By eliminating the cholesterol supply, the tumor is starved out.

The project also examined databases from hundreds of human glioblastoma patients and correlated them with the results described above.  The researchers explain: “For each patient, we examined the expression levels of genes that either neutralize the immune response or provide the tumor with a cholesterol-based energy supply. We found that patients with low expression of these identified genes lived longer, thus supporting the concept that the genes and processes identified are important to the survival of glioblastoma patients.”